Improving clinician confidence and practice behavior on the therapeutic management of microsatellite-instability high (MSI-H) gastrointestinal (GI) cancers.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 641-641
Author(s):  
Hamsa Jaganathan ◽  
Anne Roc ◽  
Wendy Turell ◽  
Russell Broaddus ◽  
Michael J. Overman
Keyword(s):  
Practice Guidelines ◽  
Checkpoint Inhibitors ◽  
Further Education ◽  
Therapeutic Management ◽  
Treatment Standards ◽  
Nccn Guidelines ◽  
Appropriate Treatment ◽  
Gi Cancers ◽  
New Treatment ◽  
Learner Responses

641 Background: With recent advances of immunotherapy and updates to practice guidelines, clinicians may be challenged in applying and managing the outcomes of new treatment standards for their patients with MSI-H GI cancers. To address this need, a one-hour education session was provided to clinicians and learner responses were evaluated to determine the areas of improvement in the therapeutic management of MSI-H GI cancers. Methods: PlatformQ Health developed and executed a 1-hour online CME program on MSI-H GI cancers, which was broadcast live in March 2018 and offered online for 6 months. The program attracted a total of 439* learners. Survey-based evaluations before (n = 338) and after education (n = 147) targeted self-reported clinician data on confidence, practice behaviors, knowledge, and competence. Results: A self-reported survey (n = 56) conducted 8-12 weeks after education reported that 50% of learners were more confident in managing patients with MSI-H GI cancers, 41% in following NCCN practice guidelines for MMR/MSI testing, and 34% in utilizing checkpoint inhibitors for MSI-H GI tumors. Competence on selecting an appropriate treatment for a patient with MSI-H colon cancer significantly improved between pre- and post-education (52% and 63%, respectively; p < 0.001). Significant improvements in knowledge regarding the latest immunotherapy data (33% at baseline to 54% post-education; p < 0.001) and available methods for determining MMR/MSI-H status (18% at baseline to 41% post-education; p < 0.001) were also observed. Conclusions: Outcomes results from education demonstrate learner improvements on facets of management of MSI-H GI cancers. Based on the analysis, further education is needed, particularly in areas of management of immune-related side effects in line with recent ASCO and NCCN guidelines, tools for determining dMMR/MSI-H status, and deciding on optimal treatment based on tumor status. *As of September 10, 2018, data collection is ongoing.

Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

2021 ◽  
Vol 19 (3) ◽  
pp. 329-359
Author(s):  
Al B. Benson ◽  
Alan P. Venook ◽  
Mahmoud M. Al-Hawary ◽  
Mustafa A. Arain ◽  
Yi-Jen Chen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Clinical Practice ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Therapy Options ◽  
Nccn Guidelines ◽  
Positive Treatment ◽  
Biomarker Testing

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation–positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

scholarly journals Gastric and Esophageal Cancers: Guidelines Updates

2021 ◽  
Vol 19 (5.5) ◽  
pp. 639-643
Author(s):  
Crystal S. Denlinger ◽  
Kristina A. Matkowskyj ◽  
Mary F. Mulcahy
Keyword(s):  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Line Treatment ◽  
Second Line ◽  
Her2 Positive ◽  
Nccn Guidelines ◽  
Esophageal Cancers ◽  
New Treatment

For the treatment of gastric and esophageal cancers, several pivotal trials—especially those evaluating immune checkpoint inhibitors (ICIs)—have altered the treatment landscape and led to changes in the NCCN Guidelines. In addition to pembrolizumab and nivolumab, new treatment options include trastuzumab-deruxtecan (T-DXd), ramucirumab, and trifluridine/tipiracil. These agents convey varying degrees of benefit depending on treatment line, PD-L1 expression, HER2 expression, and tumor histology. Recently, ICIs have been incorporated into the first-line treatment of HER2-negative advanced esophageal, gastroesophageal junction (GEJ), and gastric cancers, in addition to second-line treatment of advanced esophageal and GEJ cancer of squamous histology. T-DXd is another new second-line option for HER2-positive esophageal, GEJ, and gastric adenocarcinomas. ICIs are now moving into the adjuvant setting as well, and a new recommendation is nivolumab use after preoperative chemoradiation and surgery in patients who have residual disease identified at the time of their R0 resections.

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

2020 ◽  
Author(s):  
Guanghui Xu ◽  
Yuhao Wang ◽  
Hushan Zhang ◽  
Xueke She ◽  
Jianjun Yang
Keyword(s):  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
The Body ◽  
Low Grade ◽  
Ablative Therapies ◽  
Cancer Types ◽  
New Treatment ◽  
Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

scholarly journals Cancer Vaccines for Genitourinary Tumors: Recent Progresses and Future Possibilities

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 623
Author(s):  
Brigida Anna Maiorano ◽  
Giovanni Schinzari ◽  
Davide Ciardiello ◽  
Maria Grazia Rodriquenz ◽  
Antonio Cisternino ◽  
...  
Keyword(s):  
Cancer Vaccines ◽  
Viral Vectors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Tumor Development ◽  
Resistance Mechanisms ◽  
High Morbidity ◽  
Therapeutic Vaccines ◽  
Combination Strategies ◽  
New Treatment

Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neoplasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched PubMed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further preclinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.

scholarly journals Immune-Related Pancytopenia Induced by Anti-PD-1 Therapy – Interrupt or Continue Treatment – The Role of Immunohistochemical Examination

2019 ◽  
Vol 12 (3) ◽  
pp. 820-828 ◽  
Author(s):  
Bożena Cybulska-Stopa ◽  
Andrzej Gruchała ◽  
Maciej Niemiec
Keyword(s):  
Bone Marrow ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Positive Outcomes ◽  
Hematological Disorders ◽  
Therapeutic Outcomes ◽  
Appropriate Treatment ◽  
Programmed Death

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed death receptor-1/ligand-1 (anti-PD-1/anti-PD-L1) caused a breakthrough in oncology and significantly improved therapeutic outcomes in cancer patients. ICIs generate a specific reaction in T cells, directed against antigens on cancer cells, leading to their damage and death. Through similar or the same antigens, activated lymphocytes may also have a cytotoxic effect on healthy cells, causing development of specific adverse effects – so-called immune-related adverse events (irAEs). We present the case report of a 56 year old patient with disseminated melanoma. During treatment with immunotherapy (anti PD-1), neutropenic fever and pancytopenia occurred. Trepanobiopsy of the bone marrow was performed to determine the cause of pancytopenia. Histopathological assessment of bone marrow combined with immunophenotype investigations may explain the cause of hematological disorders occurring in the course of treatment with ICIs, and support the choice of an appropriate treatment, directly translated into positive outcomes.

Understanding relevant immune mechanisms in gastrointestinal oncology

2021 ◽  
pp. 107815522199286
Author(s):  
Bulent Cetin ◽  
Ozge Gumusay
Keyword(s):  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Gastrointestinal Cancers ◽  
Therapeutic Approaches ◽  
Cancer Treatments ◽  
Multiple Treatment ◽  
Gi Cancers ◽  
The Many

Rapid and successful drug development has resulted in multiple treatment options for gastrointestinal cancer, requiring careful decision making for individual patients. The general theme in modern immunology is that the field is moving beyond establishing the fundamental principles of immune response mechanisms to applying these propositions to understand human diseases and develop new therapies. Immunotherapy has contributed enormously to cancer treatments with a virtual explosion in novel therapeutics including checkpoint inhibitors and other recently developed immunomodulators and the development of novel therapeutic approaches. Although the majority of gastrointestinal (GI) cancers are generally considered poorly immunogenic, clinical trials have revealed that some of the patients with various gastrointestinal cancers are highly responsive to immune checkpoint inhibition-based therapies. We paid special attention to the clinical relevance of immunology and emphasized how newly developed therapies work, including what their strengths and pitfalls are. This review aims to enhance the interest of practitioners in the many specialties and subspecialties that the discipline influences and to assist them in understanding this increasing complexity.

scholarly journals The promise and perils of immunotherapy

2021 ◽  
Vol 5 (18) ◽  
pp. 3709-3725
Author(s):  
Stefanie Lesch ◽  
Saar Gill
Keyword(s):  
Checkpoint Inhibitors ◽  
Suppressive Effect ◽  
Genetically Engineered ◽  
Original Research ◽  
Future Directions ◽  
Control Tumor Growth ◽  
Engineered T Cells ◽  
Control Tumor ◽  
New Biology ◽  
New Treatment

Abstract Advances in understanding the ways in which the immune system fails to control tumor growth or prevent autoimmunity have led to the development of powerful therapeutic strategies to treat these diseases. In contrast to conventional therapies that have a broadly suppressive effect, immunotherapies are more akin to targeted therapies because they are mechanistically driven and are typically developed with the goal of “drugging” a specific underlying pathway or phenotype. This means that their effects and toxicities are, at least in theory, more straightforward to anticipate. The development of functionalized antibodies, genetically engineered T cells, and immune checkpoint inhibitors continues to accelerate, illuminating new biology and bringing new treatment to patients. In the following sections, we provide an overview of immunotherapeutic concepts, highlight recent advances in the field of immunotherapies, and discuss controversies and future directions, particularly as these pertain to hematologic oncology or blood-related diseases. We conclude by illustrating how original research published in this journal fits into and contributes to the overall framework of advances in immunotherapy.

Delayed cytokine release syndrome after neoadjuvant nivolumab: a case report and literature review

Immunotherapy ◽  
2021 ◽  
Author(s):  
Aaron T Ciner ◽  
Howard S Hochster ◽  
David A August ◽  
Darren R Carpizo ◽  
Kristen R Spencer
Keyword(s):  
Adverse Event ◽  
Checkpoint Inhibitors ◽  
Corticosteroid Treatment ◽  
Hemodynamic Instability ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Related Adverse Event ◽  
Neoadjuvant Immunotherapy ◽  
Appropriate Treatment ◽  
High Index Of Suspicion

Aim: Cytokine release syndrome (CRS) is an infrequently described immune-related adverse event of checkpoint inhibitors (CPI). CPI-induced CRS typically presents with fevers, hemodynamic instability and organ dysfunction within 2 weeks of the last treatment cycle. Case study: We report an unusual case of delayed and severe CRS occurring postoperatively in a patient with hepatic-limited metastatic colorectal cancer who received neoadjuvant immunotherapy. After a negative workup for alternative causes, he received prolonged corticosteroid treatment with symptom resolution. Conclusion: CPI-induced CRS can mimic sepsis and clinicians should maintain a high-index of suspicion to diagnose this immune-related adverse event early and initiate appropriate treatment. As use of perioperative immunotherapy increases, the potential role of surgery to trigger CRS in this case warrants further investigation.

Level of Scientific Evidence Underlying Recommendations from the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Hematologic Malignancies: Are We Moving Forward?

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Aakash Desai ◽  
Harry E Fuentes ◽  
Sri Harsha Tella ◽  
Caleb J Scheckel ◽  
Thejaswi Poonacha ◽  
...  
Keyword(s):  
Clinical Practice ◽  
National Comprehensive Cancer Network ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Scientific Evidence ◽  
Hematologic Malignancies ◽  
Level Of Evidence ◽  
Nccn Guidelines ◽  
Therapeutic Recommendations ◽  
Cancer Network

Background: National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive and widely used standard for clinical care in malignant hematology by clinicians and payers in the US. The level of scientific evidence in NCCN guidelines for malignant hematological conditions has not been recently investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common hematologic malignancies with regard to recommendations for staging, initial and salvage therapy, and surveillance. Methods: NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are: category I, high level of evidence such as randomized controlled trials with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. We compared our results with previously published results from 2011 guidelines. Results: Total recommendations increased by 16.6% from 1160 (2011) to 1353 (2020). Of the 1353 recommendations, Category 1, 2A, 2B and 3 EC were 5%, 91%, 4%, 1% while in 2011 they were 3%, 93%, 4% and 0% respectively. Recommendations with category 1 EC were found in all guidelines, except for Burkitt's Lymphoma. 6.3% of therapeutic recommendations were category 1 EC with the majority (56.4%) pertaining to initial therapy. Guidelines with highest proportions of therapeutic recommendations with category 1 EC were Multiple Myeloma (12.4%), CLL/SLL (6.9%) and AML (5.6%). Between 2011 and 2020, the proportion of category I recommendations increased significantly only in Follicular lymphoma and CLL/SLL. No category 1 EC recommendations existed in staging or surveillance. Conclusion: Recommendations issued in the 2020 NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. Despite the major advances in hematology in the past decade, this is largely unchanged. Our study underscores the urgent need and available opportunities to expand the current evidence base in malignant hematological disorders which forms the platform for clinical practice guidelines. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Pneumonitis from immune checkpoint inhibitors and COVID-19: current concern in cancer treatment

2020 ◽  
Vol 8 (2) ◽  
pp. e000952 ◽  
Author(s):  
Ernesto Rossi ◽  
Giovanni Schinzari ◽  
Giampaolo Tortora
Keyword(s):  
Adverse Event ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Clinical Symptoms ◽  
Checkpoint Inhibitors ◽  
Radiological Findings ◽  
Serious Adverse Event ◽  
Appropriate Treatment ◽  
Current Concern ◽  
Coronavirus Infection

Pneumonitis is a rare but serious adverse event caused by cancer immunotherapy. The diagnosis between COVID-19-induced pneumonia and immunotherapy-induced pneumonitis may be challenging in the era of COVID-19 outbreak. Some clinical symptoms and radiological findings of pneumonitis can be attributed to the coronavirus infection as well as to an immune-related adverse event. Identifying the exact cause of a pneumonitis in patients on treatment with immunotherapy is crucial to promptly start the most appropriate treatment. The proper management of immune checkpoint inhibitors for the risk of pneumonia must take into account a series of parameters. Accurate attention should be payed to symptoms like cough, fever and dyspnea during immunotherapy.

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